Piperidine → HCID 178430018, compound

HRID 1371187Notes

Reaction equation

HRID 1371187 reaction equation
FC1C=C[C:5]([C:8]([N:11]2CCCC2)=[CH:9]C)=CC=1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23](=O)[CH2:24][CH3:25])=[CH:19][CH:18]=1.N1C[CH2:30][CH2:29][CH2:28]1.C[C:33]1[N:38]=[C:37](Cl)[C:36]([N+:40]([O-])=O)=[C:35](Cl)[N:34]=1.C(N(CC)C(C)C)(C)C.N1CCCCC1.Cl[Sn]Cl>CN(C=O)C.Cl[Ti](Cl)(Cl)Cl.CCN(CC)CC>[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[NH:11][CH:8]([CH3:9])[CH2:5][CH:25]([C:33]3[NH:38][C:37]4=[C:29]([CH3:30])[CH:28]=[N:40][C:36]4=[CH:35][N:34]=3)[CH2:24]2)=[CH:19][CH:18]=1

Participants

11

Reactant 7

HCID 8082PiperidineHCID 24479Stannous Chloride2×HCID 31268PyrrolidineHCID 680044-FluoropropiophenoneHCID 81531DiisopropylethylamineHCID 831924,6-Dichloro-2-methyl-5-nitropyrimidineHCID 86756420HCID 86756420, compound

Product 1

HCID 178430018HCID 178430018, compoundYield 23%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
140 °C

Procedure

Using the method described in Example 30 by employing [(1-(4-fluorophenyl)prop-1-enyl]pyrrolidine (freshly prepared before use from 4′-fluoropropio phenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.65 g, 8.04 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.70 g, 8.04 mmol), N,N-diisopropylethylamine (1.4 mL, 8.04 mmol), piperidine (1.3 mL, 12.9 mmol), NEt3 (1.4 mL) and SnCl2 (24 mL of a 2 M soln in DMF). In this example the SnCl2 solution was added to the reaction mixture at 140° C. The mixture was stirred at 140° C. for an additional 16 h then the heating was discontinued and the mixture was allowed to cool to room temperature. The residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant to give 608 mg (23%) of 6-(4-fluorophenyl)-2,7-dimethyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a brown colored gummy solid. This compound (601 mg, 1.85 mmol) was dissolved in 5:15 EtOAc/MeOH (30 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.90 mL, 1.90 mmol). The solution was allowed to cool to room temperature. The resulting crystals were collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 285 mg (10%) of the title compound as a beige colored powder. Mp: >280° C. 1H HMR (DMSO-d6; 500 MHz): δ 1.68 (br s, 6), 2.32 (s, 3), 2.63 (s, 3), 4.04 (br t, 4, J=5.1), 7.43 (t, 2, J=8.7), 7.72 (dd, 2, J=7.8, 8.1), 11.93 (s, 1), 14.10 (s, 1). MS m/z: 325 (M+1 for free base). Anal. Calcd for C19H21FN4.HCl.0.3H2O: C, 62.30; H, 6.22; N, 15.30; Cl, 9.68. Found: C, 62.14; H, 6.11; N, 15.24; Cl, 9.66.

Workup

  1. customwas added to the reaction mixture at 140° C
  2. temperatureto cool to room temperature
  3. customThe residue was purified by flash chromatography on silica gel with 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-32e2b616963e40b3a495d80223e61ba3
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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